He lived decades longer than his doctors predicted when he was diagnosed with amyotrophic lateral sclerosis (ALS) - Lou Gehrig's disease - when just 21.

By the end, he had lost almost all control over every muscle in his body.

For years he's only been able to communicate through individually tailored technology, exploiting what limited muscle control he had to activate a virtual computer keyboard.

He never gave in to despair.

Instead, he thought.

And through his thoughts, he opened new horizons for humanity.

NEW YORK, NEW YORK - APRIL 12: Professor Stephen Hawking attends the New Space Exploration Initiative "Breakthrough Starshot" Announcement at One World Observatory on April 12, 2016 in New York City. Jemal Countess/Getty Images/AFP == FOR NEWSPAPERS, INTERNET, TELCOS & TELEVISION USE ONLY ==

Hawking admitted he felt "somewhat of a tragic character" after diagnosis, but he soon returned to work, securing a fellowship at Cambridge, and married Jane Wilde, with whom he had three children.

Brian Dickie, research director of the MND Association, previously said most sufferers live for less than five years - "the fact that Stephen Hawking has lived with the disease for close to 50 years makes him exceptional".

The rest of the world will always remember Hawking for his groundbreaking work on the origins of the universe, space and time - and black holes.

Much of Hawking's work centred on bringing together relativity (the nature of space and time) and quantum theory (how the smallest particles in the universe behave) to explain the creation of the universe and how it is governed.

In 1974, aged just 32, he became one of the youngest fellows of Britain's prestigious Royal Society. Five years later he became Lucasian Professor of Mathematics at Cambridge University, a post once held by Isaac Newton.

His fame moved beyond academia in 1988 with the publication of his book A Brief History of Time, which explained the nature of the universe to nonscientists, and sold millions of copies worldwide.

Stephen Hawking with his daughter Lucy. Picture: Angela Micu

Hawking's stardom was later cemented in cameos in Star Trek and The Simpsons, where he tells the rotund Homer Simpson that he likes his theory of a "doughnut-shaped universe", and may have to steal it.

Martin Rees, Britain's Astronomer Royal and a former president of the Royal Society, first met Hawking when they were both research students "and it was thought he might not live long enough to finish his PhD degree".

Rees said his survival made him a "medical marvel", but stressed that it was his work that would prove his lasting legacy.

"His fame should not overshadow his scientific contributions because even though most scientists are not as famous as he is, he has undoubtedly done more than anyone else since Einstein to improve our knowledge of gravity," he said.

Professor Stephen Hawking sits in his office at University of Cambridge, Cambridge, England, in 2012